The Clinical Significance of the CD163+ and CD68+ Macrophages in Patients with Hepatocellular Carcinoma

Abstract

Our previous study has found that the abundance of peritumoral CD68+ macrophages was associated with poor prognosis in hepatocellular carcinoma (HCC) after resection. However, CD68 staining could not discriminate the protumoral or tumoricidal subpopulations from pan-macrophages. CD163 is a marker of alternatively activated macrophages. In this study, the clinical significance of CD163+ cells in tumors and peritumoral liver tissues was evaluated in a cohort of 295 patients with HCC after curative resection. We found that the density of CD163+ cells was well correlated with that of CD68+ cells in both tumors and peritumoral liver tissues but was much more. Immunostaining on consecutive sections and flow cytometry assay on surgical resected specimens further supported the findings that the CD163+ cells was more abundant than CD68+ cells. The density of peritumoral CD68+ cells was associated with poor recurrence-free survival (RFS) and poor overall survival (OS) (P = 0.004 and P = 0.001, respectively), whereas the CD163+ cells have no prognostic values either in tumors or in peritumoral liver tissues. In another cohort of 107 HCC patients, preoperative plasma concentration of soluble form of CD163 (sCD163) was associated with active hepatitis-related factors but not associated with the markers of tumor invasion. In conclusion, both the CD163+ cells local infiltration and plasma sCD163 were of limited significance in HCC, and they were more likely markers related to active hepatitis rather than tumor progression.

Clinicopathological correlation of tumor-associated macrophages in Ewing sarcoma

“…The expression of CD163 in lymphomas, carcinomas and sarcomas has been shown to be highly specific and largely restricted to the monocyte/macrophage lineage 36 . Furthermore, CD163-positive macrophages may in some cases outnumber CD68-positive cells 37,41 as indicated by our study. Many reports have used CD163 for identification of M2 macrophages 14,16,17,31,32 .…”

Role of tumor‐associated macrophages in human malignancies: friend or foe?

“…Several reports showed positive correlations between CD68 + TAM density and poor prognosis. [45][46][47] In contrast, the density of CD163 + M2-TAMs had no prognostic value. 47 A favorable association between CD68 + TAM density and DFS and OS was also reported.…”

“…[45][46][47] In contrast, the density of CD163 + M2-TAMs had no prognostic value. 47 A favorable association between CD68 + TAM density and DFS and OS was also reported. 48 With regard to the relationship between macrophages and metastasis, the density of CD68 + HLA-DR + M1-like TAMs in HCC cases with metastasis was reportedly significantly higher than in cases without metastasis.…”

“…38 No relationship between TAMs and prognosis of patients was found in small cell lung cancer. 44 Hepatocellular carcinoma Relatively poor prognosis Several reports indicated a link between TAMs and poor prognosis, [45][46][47] but a study reported an opposite link. 48 Sites of TAM infiltration in HCC influenced prognosis differently.…”

CD68/macrosialin: not just a histochemical marker

“…[79][80][81] Except for evaluating tumorigenesis, TAM-associated CD68 expression levels can serve as a useful predictive marker for prognosis of survival of cancer patients. [82][83][84] In the phase III LYM-3001 study, Coiffier et al 85 showed a significant predictive value of a combination of low CD68 tumor expression and a genetic marker (proteasome subunit-β type-1 (PSMB1) PA11A G allele) for a longer progression-free survival of follicular lymphoma patients treated with bortezomib (proteasome inhibitor) and rituximab (anti-CD20 monoclonal antibody) vs treatment with rituximab alone. Indeed, these results suggest a potential role for assessment of CD68 expression in tumors to evaluate the efficiency and outcome prognosis of anticancer therapy.…”